• Cells are continuously exposed to chemical signals that they must discriminate between and respond to appropriately. In embryophytes, the leucine-rich repeat receptor-like kinases (LRR-RLKs) are ...signal receptors critical in development and defense. LRR-RLKs have diversified to hundreds of genes in many plant genomes. Although intensively studied, a well-resolved LRR-RLK gene tree has remained elusive.
• To resolve the LRR-RLK gene tree, we developed an improved gene discovery method based on iterative hidden Markov model searching and phylogenetic inference. We used this method to infer complete gene trees for each of the LRR-RLK subclades and reconstructed the deepest nodes of the full gene family.
• We discovered that the LRR-RLK gene family is even larger than previously thought, and that protein domain gains and losses are prevalent. These structural modifications, some of which likely predate embryophyte diversification, led to misclassification of some LRR-RLK variants as members of other gene families. Our work corrects this misclassification.
• Our results reveal ongoing structural evolution generating novel LRR-RLK genes. These new genes are raw material for the diversification of signaling in development and defense. Our methods also enable phylogenetic reconstruction in any large gene family.
The importance of whole-genome multiplication (WGM) in plant evolution has long been recognized. In flowering plants, WGM is both ubiquitous and in many lineages cyclical, each round followed by ...substantial gene loss (fractionation). This process may be biased with respect to duplicated chromosomes, often with overexpression of genes in less fractionated relative to more fractionated regions. This bias is hypothesized to arise through downregulation of gene expression through silencing of local transposable elements (TEs). We assess differences in gene expression between duplicated regions of the paleopolyploid cotton genome and demonstrate that the rate of fractionation is negatively correlated with gene expression. We examine recent hypotheses regarding the source of fractionation bias and show that TE-mediated, positional downregulation is absent in the modern cotton genome, seemingly excluding this phenomenon as the primary driver of biased gene loss. Nevertheless, the paleo subgenomes of diploid cotton are still distinguishable with respect to TE content, targeting of 24-nt-small interfering RNAs and GC content, despite approximately 60 My of evolution. We propose that repeat content per se and differential recombination rates may drive biased fractionation following WGM. These data highlight the likely importance of ancient genomic fractionation biases in shaping modern crop genomes.
Polyploidy, or whole genome duplication, has played a major role in the evolution of many eukaryotic lineages. Although the prevalence of polyploidy in plants is well documented, the molecular and ...cytological consequences are understood largely from newly formed polyploids (neopolyploids) that have been grown experimentally. Classical cytological and molecular cytogenetic studies both have shown that experimental neoallopolyploids often have meiotic irregularities, producing chromosomally variable gametes and progeny; however, little is known about the extent or duration of chromosomal variation in natural neoallopolyploid populations. We report the results of a molecular cytogenetic study on natural populations of a neoallopolyploid. Tragopogon miscellus, which formed multiple times in the past 80 y. Using genomic and fluorescence in situ hybridization, we uncovered massive and repeated patterns of chromosomal variation in all populations. No population was fixed for a particular karyotype; 76% of the individuals showed intergenomic translocations, and 69% were aneuploid for one or more chromosomes. Importantly, 85% of plants exhibiting aneuploidy still had the expected chromosome number, mostly through reciprocal monosomy-trisomy of homeologous chromosomes (1:3 copies) or nullisomy-tetrasomy (0:4 copies). The extensive chromosomal variation still present after ca. 40 generations in this biennial species suggests that substantial and prolonged chromosomal instability might be common in natural populations after whole genome duplication. A protracted period of genome instability in neoallopolyploids may increase opportunities for alterations to genome structure, losses of coding and noncoding DNA, and changes in gene expression.
BACKGROUND:Studies that have attempted to define the incidence of aspiration or pulmonary complications during sedation/anesthesia of children with respect to nil per os (NPO) status or other factors ...are difficult because of the relatively infrequent rate of these complications.
METHODS:The Pediatric Sedation Research Consortium consists of 42 participating institutions with elective sedation services that submit consecutive patient encounter information to a central database. The authors evaluated aspiration episodes and a combined outcome of major adverse events (defined as aspiration, death, cardiac arrest, or unplanned hospital admission) with respect to NPO status, American Society of Anesthesiologists physical status, age, propofol use, procedure types, and urgency of the procedure.
RESULTS:A total of 139,142 procedural sedation/anesthesia encounters were collected between September 2, 2007 and November 9, 2011. There were 0 deaths, 10 aspirations, and 75 major complications. NPO status was known for 107,947 patients, of whom 25,401 (23.5 %) were not NPO. Aspiration occurred in 8 of 82,546 (0.97 events per 10,000) versus 2 of 25,401 (0.79 events per 10,000) patients who were NPO and not NPO, respectively (odds ratio, 0.81; 95% CI, 0.08 to 4.08; P = 0.79). Major complications occurred in 46 of 82,546 (5.57 events per 10,000) versus 15 of 25,401 (5.91 events per 10,000) (odds ratio, 1.06; 95% CI, 0.55 to 1.93; P = 0.88). Multivariate adjustment did not appreciably impact the effect of NPO status.
CONCLUSIONS:The analysis suggests that aspiration is uncommon. NPO status for liquids and solids is not an independent predictor of major complications or aspiration in this sedation/anesthesia data set.
Meristems contain groups of indeterminate stem cells, which are maintained by a feedback loop between
(
) and
(
) signaling. CLV signaling involves the secretion of the CLV3 peptide and its ...perception by a number of Leucine-Rich-Repeat (LRR) receptors, including the receptor-like kinase CLV1 and the receptor-like protein CLV2 coupled with the CORYNE (CRN) pseudokinase. CLV2, and its maize ortholog FASCIATED EAR2 (FEA2) appear to function in signaling by CLV3 and several related CLV3/EMBRYO-SURROUNDING REGION (CLE) peptide ligands. Nevertheless, how signaling specificity is achieved remains unknown. Here we show that FEA2 transmits signaling from two distinct CLE peptides, the maize CLV3 ortholog ZmCLE7 and ZmFON2-LIKE CLE PROTEIN1 (ZmFCP1) through two different candidate downstream effectors, the alpha subunit of the maize heterotrimeric G protein COMPACT PLANT2 (CT2), and ZmCRN. Our data provide a novel framework to understand how diverse signaling peptides can activate different downstream pathways through common receptor proteins.
We studied the clinical and economic impact of a protocol encouraging the use of fidaxomicin as a first-line drug for treatment of Clostridium difficile infection (CDI) in patients hospitalized ...during a 2-year period. This study evaluated patients who received oral vancomycin or fidaxomicin for the treatment of CDI during a 2-year period. All included patients were eligible for administration of fidaxomicin via a protocol that encouraged its use for selected patients. The primary clinical endpoint was 90-day readmission with a diagnosis of CDI. Hospital charges and insurance reimbursements for readmissions were calculated along with the cost of CDI therapy to estimate the financial impact of the choice of therapy. Recurrences were seen in 10/49 (20.4%) fidaxomicin patients and 19/46 (41.3%) vancomycin patients (P = 0.027). In a multivariate analysis that included determinations of severity of CDI, serum creatinine increases, and concomitant antibiotic use, only fidaxomicin was significantly associated with decreased recurrence (adjusted odds ratio aOR, 0.33; 95% confidence interval CI, 0.12 to 0.93). The total lengths of stay of readmitted patients were 183 days for vancomycin and 87 days for fidaxomicin, with costs of $454,800 and $196,200, respectively. Readmissions for CDI were reimbursed on the basis of the severity of CDI, totaling $151,136 for vancomycin and $107,176 for fidaxomicin. Fidaxomicin drug costs totaled $62,112, and vancomycin drug costs were $6,646. We calculated that the hospital lost an average of $3,286 per fidaxomicin-treated patient and $6,333 per vancomycin-treated patient, thus saving $3,047 per patient with fidaxomicin. Fidaxomicin use for CDI treatment prevented readmission and decreased hospital costs compared to use of oral vancomycin.
We sought to use a large database of prospectively collected data on pediatric sedation and/or anesthesia for diagnostic and therapeutic procedures to delineate the nature and the frequency of ...adverse events that are associated with sedation/anesthesia care for procedures that are performed outside the operating room in children.
Data were collected by the Pediatric Sedation Research Consortium, a collaborative group of 35 institutions that are dedicated to improving sedation/anesthesia care for children internationally. Members prospectively enrolled consecutive patients who were receiving sedation or anesthesia for procedures. Data on demographics, primary illness, coexisting illness, procedure performed, medications used, outcomes, airway interventions, and adverse events were collected and reported on a Web-based data collection tool.
A total of 26 institutions submitted data on 30,037 sedation/anesthesia encounters during the study period from July 1, 2004, to November 15, 2005. Serious adverse events were rare in the institutions involved in this study; there were no deaths. Cardiopulmonary resuscitation was required once. Less serious events were more common with O2 desaturation below 90% for > 30 seconds, occurring 157 times per 10000 sedations. Stridor and laryngospasm both occurred in 4.3 per 10,000 sedations. Unexpected apnea, excessive secretions, and vomiting had frequencies of 24, 41.6, and 47.2 per 10,000 encounters, respectively.
Our data indicate that pediatric sedation/anesthesia for procedures outside the operating room is unlikely to yield serious adverse outcomes in a collection of institutions with highly motivated and organized sedation services. However, the safety of this practice depends on the systems' ability to manage less serious events.
Baobabs (Adansonia) are a cohesive group of tropical trees with a disjunct distribution in Australia, Madagascar, and continental Africa, and diverse flowers associated with two pollination modes. We ...used custom-targeted sequence capture in conjunction with new and existing phylogenetic comparative methods to explore the evolution of floral traits and pollination systems while allowing for reticulate evolution. Our analyses suggest that relationships in Adansonia are confounded by reticulation, with network inference methods supporting at least one reticulation event. The best supported hypothesis involves introgression between Adansonia rubrostipa and core Longitubae, both of which are hawkmoth pollinated with yellow/red flowers, but there is also some support for introgression between the African lineage and Malagasy Brevitubae, which are both mammal-pollinated with white flowers. New comparative methods for phylogenetic networks were developed that allow maximum-likelihood inference of ancestral states and were applied to study the apparent homoplasy in floral biology and pollination mode seen in Adansonia. This analysis supports a role for introgressive hybridization in morphological evolution even in a clade with highly divergent and geographically widespread species. Our new comparative methods for discrete traits on species networks are implemented in the software PhyloNetworks.
We used a large database of prospectively collected data on pediatric sedation/anesthesia outside the operating room provided by a wide range of pediatric specialists to delineate the nature and ...frequency of adverse events associated with propofol-based sedation/anesthesia care.
Data were collected by the Pediatric Sedation Research Consortium, a collaborative group of institutions dedicated to improving sedation/anesthesia care for children internationally. Members prospectively enrolled consecutive patients receiving sedation or sedation/anesthesia for procedures. The primary inclusion criterion was the need for some form of sedation/anesthesia to perform a diagnostic or therapeutic procedure outside the operating room. There were no exclusion criteria. Data on demographics, primary illness, coexisting illness, procedure performed, medications used, procedure and recovery times, medication doses outcomes of anesthesia, airway interventions and adverse events were collected and reported using web-based data collection tool. For this study, we evaluated all instances where propofol was used as the primary drug in the sedation/anesthesia technique.
Thirty-seven locations submitted data on 49,836 propofol sedation/anesthesia encounters during the study period from July 1, 2004 until September 1, 2007. There were no deaths. Cardiopulmonary resuscitation was required twice. Aspiration during sedation/anesthesia occurred four times. Less serious events were more common with O(2) desaturation below 90% for more than 30 s, occurring 154 times per 10,000 sedation/anesthesia administrations. Central apnea or airway obstruction occurred 575 times per 10,000 sedation/anesthesia administrations. Stridor, laryngospasm, excessive secretions, and vomiting had frequencies of 50, 96, 341, and 49 per 10,000 encounters, respectively. Unexpected admissions (increases in levels of care required) occurred at a rate of 7.1 per 10,000 encounters. In an unadjusted analysis, the rate of pulmonary adverse events was not different for anesthesiologists versus other providers.
We report the largest series of pediatric propofol sedation/anesthesia for procedures outside the operating room. The data indicate that propofol sedation/anesthesia is unlikely to yield serious adverse outcomes in a collection of institutions with highly motivated and organized sedation/anesthesia services. However, the safety of this practice is dependent on a system's ability to manage less serious events. We propose that our data suggest variables for training and credentialing providers of propofol sedation/anesthesia and the system characteristics that promote safe use of this drug.
Wake Atoll is an isolated chain of three islets located in the Western Pacific. Included in its endemic flora is a representative of the genus Gossypium colloquially referred to as Wake Island ...cotton. Stanley G. Stephens pointed out that “Wake Island cotton does not resemble closely either the Caribbean or other Pacific forms.” Taking into consideration morphological distinctions, the geographic isolation of Wake Atoll, and newly generated molecular data presented here, we conclude that the cottons of Wake Atoll do in fact represent a new species of Gossypium, here named Gossypium stephensii. This name is chosen to commemorate the eminent natural historian, evolutionary geneticist, and cotton biologist, S. G. Stephens.
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